Immunology xi immunodeficiency
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Immunology xi immunodeficiency






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Immunology xi immunodeficiency Immunology xi immunodeficiency Presentation Transcript

  • Imunodeficiency states
    • Primary
      • Caused by defined genetic defects
      • Usually rare, but severe (exception: IgA deficiency)
    • Se condary
      • Consequence of so m e other disease, treatment, environmental factors…
      • Usually frequent, but usually clinically mild (ex c eptions: HI V disease, secondary aganulocytosis).
  • Severe combined immunodeficiency (SCID)
    • Early clinical manifestation (weeks-months)
    • Severe and complicated infections affecting respiratory and gastrointestinal tract and the skin
    • Failure to thrive
    • Frequent diarrhea
    • Usually lymphocytopenia
    • T-cell def i ciency, B cell present in some patients
    • Decreased immunoglobulin levels
  • SCID, t-GVHR, generalised BCG-itis View slide
  • SCID infections caused by atypical patogens
    • Pneumocystis pneumonia
    • Cytomegalovirus pneumonitis
    • Disseminated BCG-itis
    • Infections caused by atypical mycobacteria
    • Candidiasis of oropharynx, skin
    View slide
  • Pa tient with SC ID
  • Immunoglobulin Deficiencies Clinical manifestations begins at 6-12 months (or late). Susceptibility to infection by encapsulated bacteria (Pneumococcus, Haemophilus) . Respiratory tract predominantly affected; patients suffer from recurrent otitis media,bronchitis, sinusitis, pneumonia . Some patients also suffer from meningitis or chronic diarrhea .
  • X-linked agammaglobulinemia
    • Only boys affected
    • Clinical manifestation usually begins at 6-12 months
    • Severe and complicated respiratory tract infections.
    • Very low levels of all immunoglobulin isotypes.
    • B-cell not detected
  • Common variable immunodeficiency (CVID)
    • Both sexes affected
    • Clinical manifestation initiates at any age
    • Frequent and severe respiratory tract infections
    • P r oneness to autoimmune diseases
    • Vari ab le decrea s e of immunoglobulin isotypes, usually markedly decreased I gA and I gG leves
    • B-lymphocy t es usually present
  • Selective IgA deficiency
    • Frequency: 1:400
    • Usually only mild manifestation
    • Predominantly respiratory tract infections
    • Patients are prone to autoimmune diseases
    • Beware of anti-IgA antibodies that can cause a severe anaphylactic reaction after artificial IgA administration (by blood, immunoglobulin derivates)!
    • T-cell Deficiences
    • Early onset of clinical manifestation .
    • Extreme susceptibility to viral, fungal, mycobacterial, and protozoal infections .
    • - Respiratory system most frequently affected, but also other systems can be involved .
  • DiGeorge syndrome
    • Defect in embryonic development of the 3rd and 4th pharyngeal pouches.
    • Cardiovascular defects
    • Hypoparathyroidism  hypocalcemia  seizures
    • Thymic hypoplasia  T cell def i ciency
    • Typical facies: hypertelorism, micrognatia, low-set, posterior rotated ears.
  • DiGeorge syndrom e
  • DiGeorge syndrom e
  • Complement deficiencies
    • Deficiency of C1-C4: autoimmune systemic disorders, susceptibility to bacterial infections
    • Deficiency C5-C9: susceptibility to bacterial infections, mainly to meningococcal meningitis
    • Defici e ncy of C1 INH: hereditary angioedema
  • Hereditary angioedema
    • Deficiency of C1 inhibitor (C1 INH)
    • Uncontrolled activation of the complement system after trauma, infection, surgical operation....
    • Vasoactive peptides ( bradykinin, C3a,C5a) cause increased vascular permeability
    • Oedema of the skin, respiratory tract (dyspnoe), gastrointestinal tract (cramps, vomiting)
  • Phagocytic dysfunction
    • Early onset of clinical manifestation
    • Susceptibility to bacterial and fungal infections
    • A b scess formation, mainly of the skin, periproctal area, liver, but any area may be affected.
  • Chronic granulomatous disease
    • Recurrent abscesses mainly of the liver, lungs, periproctal area, suppurative lymphadenitis, osteomyelitis
    • Infections are caused mainly by catalase-positive organisms: St. aureus, Candida sp. , Serratia marcescens
    • Usually early onset of symptoms
    • Production of reactive metabolites of oxygen is disturbed (defect of NADPH oxidase)
  • Wiskott-Aldrich syndrome
    • X-linked disease
    • Thrombocytopemia  bleeding tendency
    • Severe eczema
    • Immunodef i ciency
    • Severe allergic and autoimmune manifestations
    • B-cell lymphomas
  • Wiskott-Aldrich syndrom e
  • Ataxia telangiectasia
    • Autosomal recessive
    • Progressive ce r ebe llar ataxia
    • Tela n giectasis especially on ear lobes and conjunctival sclera
    • Immunodeficiency
    • Frequent tumors
    • Cause: m utation in ATM gene
  • A taxia telangiectasia
  • Treatment of primary immunodefciencies
    • SCID and other severe immunodeficiencies: bone marrow transplantation, gene therapy in some cases.
    • Antibody deficiencies: immunoglobulin replacement
    • Antibiotic prohylaxis
  • Clinical use of non-specific immunoglobulin derivates
    • Types of derivates:
      • „ Normal immunoglobulin“ - for intramuscular use . Used very rarely at present bcause only low dose can be given..
      • Intravenous immunoglobulins , subcutaneous immunoglobulins - can be used in high doses
    • Indications:
      • Replacement treatment in patients with antibody deficiencies
      • Prophylaxis of infections against which there is no specific immunoglobulin derivate (hepatitis A)
      • High doses of i.v. immunoglobulins are used in autoimmune diseases , systemic vasculitic diseases.
  • Causes of secondary immunodeficiency
    • Metabolic - ur e mia, diabetes, malnutr it ion
    • Iatrogenic – cytostatics, immunosuppressants
    • Malignat tumors
    • Viral infections - HIV , CMV , measles, infectious mononucleosis
    • Splenectomy
    • Stres s
    • Injuries, operations, general anestes ia
  • Imunodeficiency after splenectomy
    • Disturbed phagocytosis, decreased production of antibodies.
    • The most severe complication is hyperacute pneumococal sepsis.
    • Prevention: vaccination against Pneumococcus, Haemophilus infl. B, Meningococcus. PNC pro p hylaxis.
  • Secondary hypogammaglobulinemia
    • Decreased production of immunoglobulins
      • Chronic lymphatic leukemia
      • Lymphoma
      • Myeloma
    • Loss of immunoglobulins
      • Nephrotic syndrome
      • Exudative enteropathy
  • Ways of transmission
    • Sexual
    • Parenteral – intravenous drug addicts
    • previously blood products
    • 3. Vertical – mother to child – transplacental, during delivery, by brestfeeding
  • Infe ction of CD4+ cell by HIV
  • HIV Cy cle
  • Classification of HIV disease (CDC)
    • 3 clinical categories
    • A Asymptomatic disese
    • B „small“ opportunistic infections
    • C „big“ opportunistic infections and other states that define AIDS
  • Clinical category A
    • Accute (primary) HIV infection
    • Asymptomatic HIV infection
    • Persistent generalised lymphadenopathy (PGL)
    • Acute retroviral syndrome, („mononucleosis-like syndrome“)
    • Present in 50-70% patients
    • 2-6 weeks after infection
  • Clinical presentaioon of HIV primoinfection
    • Fever, lympadenopathy, pharyngitis
    • Rash
    • Myalgia, arthralgia, diarrhoea, cephalea
    • nausea, vomiting
    • thrush
    • Neurologic symptoms
    • A phtous stomatitis
  • Perzistent generalized lympadenopathy -
    • More than 3 months
    • 1/3 HIV-infected persons
    • Lymph nodes 0,5-2,0 cm, painless
  • Clinical category B
    • Fever >38,5 C more than 1 month
    • Diarrhoea more than 1 month
    • Oropharyngea candidiasis
    • Vulvovaginal candidiasis
    • (chronic or difficult to treat)
    • Recurrent herpes zoster
  • Clinical category C (AIDS)
    • Pneumocystis pneumonia
    • Brain abscess caused by toxoplasma
    • Esofageal, tracheal, bronchial or lung candidiasis
    • Chronic anal herpes, herpetic bronchitis, pneumonia
    • CMV retinitis, generalized CMV infection
    • Progressive multifocal leukoecephalopathy
    • Mycobacterial infections
  • Opportunistic Infections in AIDS Patients - Pneumonia due to Pneumocystis jiroveci ( carinii ) - Toxoplasma brain abscess - Cytomegalovirus infection (retinitis, colitis) - Mycobacterial infections - Herpes virus and Varicella-Zoster infections
  • Clinical category C ( AIDS ) - tumors
    • Kaposhi sarcoma
    • Brain lymphoma
  • Kaposh i sar coma
  • Kaposiho sarkom
  • Wasting syndrome
  • Treatment of HIV-disease
    • Antiretroviral
      • Nucleoside inhibitors of reverse transcriptase : azidothymidin (syn. zidovudin), didanosin, zalcitabin, stavudin, lamivudin
      • Nonnucleoside inhibitors of reverse transcriptase : Nevirapin, delavirdin, efavirenz
      • HIV protease inhibitors : Saquinavir, ritonavir, indinavir
    • Prophylaxis of Pneumocystis carinii pneumonia (co-trimoxazol), antiviral and antimycotic antibiotics
  • Strategy of treatment
    • HAART - Highly
    • Active
    • Anti
    • Retroviral
    • Therapy
    • Mega-HAART
  • Diagnos is of HIV infe ction
    • Detection of anti-viral antibodies
      • ELISA
      • Western blott
    • Detection of antigen p 24